Dicyclohexylcarbodiimide → HCID 54763972, compound

HRID 469448Notes

Reaction equation

HRID 469448 reaction equation
[C:1]([C:4]1[S:5][CH:6]=[CH:7][C:8]=1[NH:9][CH:10]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:11]([OH:13])=[O:12])(=[O:3])[CH3:2].[N:20]12[CH2:27][CH2:26][CH:23]([CH2:24][CH2:25]1)[C@@H:22](O)[CH2:21]2.C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>C1COCC1>[N:20]12[CH2:27][CH2:26][CH:23]([CH2:24][CH2:25]1)[C@@H:22]([O:12][C:11](=[O:13])[CH:10]([NH:9][C:8]1[CH:7]=[CH:6][S:5][C:4]=1[C:1](=[O:3])[CH3:2])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH2:21]2

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 914043-Quinuclidinol, (-)-HCID 58557018HCID 58557018, compound

Product 1

HCID 54763972HCID 54763972, compoundYield 18.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2-(2-acetylthiophen-3-ylamino)-2-phenylacetic acid (I4) (188 mg, 0.68 mmol), (R)-quinuclidin-3-ol (104 mg, 0.82 mmol), HOBT (125 mg, 0.82 mmol) and DCC (169 mg, 0.82 mmol) in dry THF (8 ml) was stirred at room temperature overnight. THF was evaporated, and the crude product was taken up with EtOAc and washed twice with 2M K2CO3. The organic phase was dried (Na2SO4), filtered and evaporated to dryness. The crude product was purified by preparative HPLC. The fractions containing the product were combined and evaporated under vacuum. The residue was dissolved in 2M K2CO3 and extracted twice with EtOAc to obtain (2-acetyl-thiophen-3-ylamino)-phenyl-acetic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)ester (48 mg, 18% yield).

Workup

  1. customTHF was evaporated
  2. washwashed twice with 2M K2CO3
  3. dry with materialThe organic phase was dried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customThe crude product was purified by preparative HPLC
  7. additionThe fractions containing the product
  8. customevaporated under vacuum
  9. dissolutionThe residue was dissolved in 2M K2CO3
  10. extractionextracted twice with EtOAc

Sources & evidence

ORD record
ord-0ef54709494248c6be873ba59e75751f
Source dataset
uspto-grants-2014_01
Patent number
US08629160B2

Reaction notes

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